Exploring the Bidirectional Link Between Graves’ Disease and Gut Microbiome: New Insights Into the Thyroid–Gut Axis Original paper
-
Autoimmune Diseases
Autoimmune Diseases
Autoimmune disease is when the immune system mistakenly attacks the body's tissues, often linked to imbalances in the microbiome, which can disrupt immune regulation and contribute to disease development.
Microbiome Signatures identifies and validates condition-specific microbiome shifts and interventions to accelerate clinical translation. Our multidisciplinary team supports clinicians, researchers, and innovators in turning microbiome science into actionable medicine.
Karen Pendergrass
What was studied?
This study investigated the bidirectional causal relationship between Graves’ Disease (GD) and the gut microbiome. Utilizing Mendelian randomization (MR), it examined how alterations in the gut microbiome might influence GD and vice versa, supporting the thyroid–gut axis (TGA) concept. Genome-wide association study (GWAS) summary datasets, which analyze millions of genetic variants across diverse populations to identify associations between genetic markers and specific traits, were sourced from international consortiums to evaluate these interactions.
Who was studied?
The study involved two large datasets. Gut microbiome data included 18,340 samples spanning diverse ethnic groups (European, Middle Eastern, East Asian, Hispanic/Latin American, and African American), while GD data included 212,453 samples of Asian ethnicity, sourced from Biobank Japan. These comprehensive datasets were analyzed to identify instrumental variables linking genetic variants to gut microbiome composition and GD susceptibility.
What were the most important findings?
The study established a bidirectional causal relationship between Graves’ disease (GD) and the gut microbiome, identifying key microbial associations that act as either risk or protective factors. Risk factors for GD included the classes Deltaproteobacteria (odds ratio [OR] = 3.603) and Mollicutes, as well as the genera Ruminococcus torques group, Oxalobacter, and Ruminococcaceae UCG 011. Protective associations were observed for the family Peptococcaceae and the genus Anaerostipes (OR = 0.489). Furthermore, GD was found to alter gut microbiome composition, increasing the abundance of genera like Anaerofilum (OR = 1.584) and reducing taxa such as the Clostridium innocuum group (OR = 0.918) and Sutterella (OR = 0.953). These findings highlight the regulatory activity of the thyroid–gut axis (TGA) and provide strong evidence for its involvement in GD pathogenesis.
What are the greatest implications of this study?
The findings underscore the critical role of the gut microbiome in GD pathogenesis and its reciprocal interaction with thyroid health. Identifying specific microbial taxa as risk or protective factors offers actionable insights for microbiome-targeted interventions (MBTIs), such as probiotics or dietary modifications, tailored to mitigate GD risk or progression. The bidirectional relationship between GD and the gut microbiome highlights the need for integrated approaches addressing both thyroid and gut health. These results could guide the development of precision medicine strategies, leveraging the gut microbiome to modulate immune responses and improve clinical outcomes for patients with GD. This research also establishes a foundational understanding of major microbial associations (MMAs) within the TGA, paving the way for future therapeutic innovations. Further, this study establishes a methodological precedent for using Mendelian Randomization to discern causal effects in microbiome-related research.
Microbiome-Targeted Interventions (MBTIs)
Microbiome Targeted Interventions (MBTIs) are cutting-edge treatments that utilize information from Microbiome Signatures to modulate the microbiome, revolutionizing medicine with unparalleled precision and impact.
Major Microbial Associations (MMAs)
Major Microbial Associations (MMAs) are fundamental in understanding disease-microbiome interactions and play a crucial role in advancing microbiome-targeted interventions aimed at treating or preventing diseases through microbial modulation.